Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment.
J Allergy Clin Immunol
; 152(5): 1179-1195, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37315812
ABSTRACT
BACKGROUND:
Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity.OBJECTIVES:
This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab.METHODS:
Participants (n = 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 21), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping.RESULTS:
At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in TH17-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed.CONCLUSIONS:
Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for TH17 cells, neutrophils, and complement activation as potential mechanisms to explain these findings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Dermatite Atópica
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2023
Tipo de documento:
Article